Since the first recognition of beryllium disease (Be) in the early 1940's, about 800 cases have been reported in this country and with the increasing use of Be and its alloys in various industries, this disease will continue to present an important occupational health hazard. The disease occurs in acute and chronic form and in both, lung injury dominates the clinical pathologic picture, however, the pathogenic mechanisms are not yet clear. While the direct toxic effect of Be is responsible for the acute form, in the chronic form, delayed hypersensitivity (cellular immunity) mechanisms have been suggested to play an important role. In the past, the evidence for the latter mechanism has been largely indirect, inconclusive and based primarily on the results of skin tests with Be salts. To provide a more direct evidence, we recently studied the in vitro interaction between lymphocytes of patients with the chronic disease and Be SO4 using the currently accepted parameters for cellular immunity such as blast transformation, uptake of tritiated thymidine and release of migration inhibitory factor (MIF). Of the 34 patients studied, 70 percent showed significant positive results and a good correlation with clinical severity of the disease. In the proposed project, we wish to further explore the cellular immune mechanisms, both on a clinical and experimental level. The clinical studies will include frequent in vitro studies on patients' lymphocytes for correlation with clinical state, exploration of reactions with various proteins (serum, skin and lung) complexed with Be ions, and an annual study of workers (about 600) at the Brush Beryllium Co. in Ohio with the in vitro tests to determine the incidence and significance of positive reactions. The experimental studies should include attempts to produce the disease in either inbred guinea pigs or rats by intratracheal injections of Be salts, similar in vitro studies of lymphocytes, study of the effect of suppressing cellular immunity and of passive transfer of sensitized lymphocytes. These studies should yield valuable information towards a better understanding of this important occupational disease.